ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

The machine learning is used increasingly and widely in acupuncture prescription optimization, intelligent treatment and precision medicine, and has obtained a certain achievement. But, there are still some problems remained to be solved such as the poor interpretability of the model, the inconsistency of data quality of acupuncture research, and the clinical application of constructed models. Researches in future should focus on the acquisition of high-quality clinical and experimental data sets, take various machine learning algorithms as the basis, and construct professional models to solve various problems, so as to drive the high-quality development of acupuncture research.
Acupuncture Therapy/trends* ; Machine Learning ; Humans ; Algorithms

OBJECTIVE: To evaluate the feasibility and short-term effectiveness of three-dimensional (3D)-printed customized porous acetabular components for reconstruction of extensive acetabular bone defects during primary total hip arthroplasty (THA). METHODS: The clinical data of 8 patients with extensive acetabular bone defects, who were treated with 3D-printed individualized porous acetabular components between July 2018 and January 2022, were retrospectively analyzed. The cohort comprised 4 males and 4 females with an average age of 48 years ranging from 34 to 56 years. Acetabular bone defects were classified as Paprosky type ⅢA in 3 cases and type ⅢB in 5 cases. The causes of acetabular destruction were hip tuberculosis (5 cases), pigmented villonodular synovitis (2 cases), and syphilitic arthritis (1 case). Visual analogue scale (VAS) score and Harris hip score (HHS) were used to evaluate the pain relief and hip function before and after operation. Reconstruction outcomes were further assessed by imaging results [X-ray film and Tomosynthesis Shimadzumetal artefact reduction technology (T-SMART)], and the mechanical properties were evaluated by finite element analysis. RESULTS: The operation time ranged from 174 to 195 minutes (mean, 187 minutes), and intraoperative blood loss ranged from 390 to 530 mL (mean, 465 mL). All 8 patients were follow-up 26-74 months (mean, 44 months). Among the 5 patients with tuberculosis, none experienced postoperative recurrence. At last follow-up, the VAS score was 0.3±0.5 and the HHS score was 87.9±3.7, both significantly improved compared to preoperative values ( t=25.170, P<0.001; t=-28.322, P<0.001). X-ray films at 2 years after operation demonstrated satisfactory matching between the 3D-printed customized acetabular component and the acetabulum. The postoperative center of rotation of the operated hip was shifted by (2.1±0.5) mm horizontally and (2.0±0.7) mm vertically relative to the contralateral side, with both offsets showing significant differences compared to preoperative values ( t=24.700, P<0.001; t=55.230, P<0.001). T-SMART imaging showed satisfactory osseointegration at the implant-host bone interface. No complications such as aseptic loosening or screw breakage was observed during follow-up. Finite element analysis showed that the acetabular component had good mechanical properties. CONCLUSION The application of 3D-printed individualized porous acetabular components in the reconstruction of extensive acetabular bone defects demonstrated precise anatomical reconstruction, stable mechanical support, and good functional performance in short-term follow-up, offering a potential alternative for acetabular defect reconstruction in primary THA.
Humans ; Middle Aged ; Male ; Female ; Printing, Three-Dimensional ; Arthroplasty, Replacement, Hip/instrumentation* ; Acetabulum/diagnostic imaging* ; Adult ; Follow-Up Studies ; Retrospective Studies ; Hip Prosthesis ; Prosthesis Design ; Porosity ; Treatment Outcome ; Plastic Surgery Procedures/methods*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength

ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.

Objective: To analyze the status and correlation between screen time, screen behavior type, and anxiety, depression among children and adolescents in Jiangxi Province, so as to provide a basis for effective intervention measures. Methods: Using the method of stratified random sampling, 8 851 primary and secondary school students in 11 districts of Jiangxi Province were investigated by questionnaire during September to December in 2020. Anxiety and depression status were investigated using the State Trait Anxiety Inventory (STAI) and the Center for Epidemiological Studies Depression Scale for Children(CES-DC), respectively. Single factor analysis using χ 2-test, t-test,analysis of variance,and multivariate analysis using generalized linear models. Results: On school days and weekends, 4.7% and 20.4% of primary and secondary school students in Jiangxi Province had a total screen time of over 2 hours per day, respectively. The weighted scores of the total screen time (primary school students: 1.88± 0.68, junior middle school students: 1.96±0.71, high school students: 2.03±0.80) and time spent for playing video games (primary school students: 1.51±0.64, junior middle school students: 1.62±0.69, high school students: 1.68±0.75) daily showed an upward trend with the increase of educational stage ( F =31.48, 42.13), and with significantly higher in boys (1.97±0.74, 1.66± 0.72) than girls (1.93±0.72, 1.53±0.66)( t =2.48, 9.07)( P <0.05). The average scores of state anxiety and trait anxiety were (42.20±9.05) and (40.65±9.85), which showed an upward trend with the increase of educational stage ( F =168.12, 241.98 ), and were higher in girls than boys ( t =6.63, 8.48)( P <0.01). The average score of depression was (11.99±11.00), which was lower in elementary school students than middle school students and high school students ( F =136.42), with significantly higher in girls ( t =6.85)( P <0.01). On school days, with the increase of total screen time and time spent for playing video games daily, the risk of state anxiety, trait anxiety, and depression among primary and secondary school students significantly increased ( OR = 6.70- 818.98, P <0.01). On weekends, among primary and secondary school students, the total screen time of >1-2 hours daily reduced the risk of state anxiety ( OR =0.30). The risk of developing trait anxiety among students playing video games for more than 2 hours daily was 2.50 times higher than those without screen behavior ( OR =2.50). The risk of developing depression with a total screen time of more than 2 hours daily was 3.15 times higher those whithout screen behavior ( OR =3.15). The risk of developing depression among students playing video games >0-1, >1-2, >2 h daily was 2.14, 2.50, 4.90 times that of those without screen behaviors ( OR =2.14, 2.50, 4.90), and showed an upward trend with the increase of educational stage ( P <0.05). Conclusions Screen behaviors of primary and middle school students in Jiangxi Province are positively associated with the risk of anxiety and depression, but the total daily video time of >1-2 h on weekends was negatively associated with state anxiety. It is necessary to control the screen time as much as possible and reduce the risk of anxiety and depression.